Safety, adherence, and compliance in a RCT of supervised exercise training among persons with multiple sclerosis who have slowed cognitive processing speed

Abstract

Background

Safety, adherence, and compliance have been poorly-characterized in randomized controlled trials (RCTs) of exercise training within multiple sclerosis (MS) research. The MoXFo initiative recently proposed standard criteria for defining exercise safety, adherence, and compliance, yet these criteria have infrequently been applied within an exercise training RCT involving people with MS.

Objective

This study applied published criteria for characterizing safety, adherence, and compliance within a RCT that compared 12-weeks of supervised treadmill walking exercise (TMWX) training (intervention condition) with 12-weeks of stretching-and-toning (active control condition) among fully-ambulatory persons with MS who demonstrated slowed cognitive processing speed (CPS).

Methods

37 fully-ambulatory persons with MS with slowed CPS were randomly assigned into the TMWX condition (n = 18) or active control condition (n = 19). We defined safety as number of adverse events (AEs); adherence as number and rate of sessions attended; and compliance as number and rate of sessions completed as prescribed. We further examined potential baseline predictors of adherence and compliance rates using correlations and regressions.

Results

There were 10 non-serious AEs that were generally unrelated to the conditions (e.g., non-injurious falls that took place outside of the study, temporary illnesses). On average, participants attended 25.8 of 36 possible sessions (i.e., adherence rate=71.5 %). On average, participants completed 25.2 of the 36 possible sessions as prescribed (i.e., compliance rate = 70.0 %) and 97.7 % of attended sessions as prescribed. Of note, adherence did not differ by condition, though relative compliance rate was significantly higher among those who underwent the control condition (p = .03). In the overall sample, regressions identified no significant predictors of adherence, but higher agreeableness predicted higher relative compliance rate. Within the TMWX condition, longer disease duration and lower anxiety predicted higher adherence, and lower impact of MS on physical and mental domains and higher agreeableness predicted higher relative compliance rate. Within the control condition, lower brainstem functional systems scores and lower neuroticism predicted higher adherence, and no baseline variables predicted relative compliance rate.

Conclusions

The safety, adherence, and compliance data, as defined based on recent recommendations, suggest that the TMWX and stretching conditions are safe, feasible, and attainable among fully-ambulatory, persons with MS with slowed CPS. The heterogeneous pattern of baseline variables that predicted adherence and compliance rates overall and in the respective experimental conditions warrant replication in larger MS samples.

Introduction

Exercise training, defined as planned, structured, repetitive physical activity for improving or maintaining physical fitness (Mansoubi et al., 2023), is associated with numerous benefits among persons with multiple sclerosis (MS). Systematic reviews and meta-analyses report on exercise training-related improvements in physical fitness, mobility, balance, fatigue, depressive symptoms, and cognition in this population (RW Motl et al., 2017). Furthermore, additional evidence suggests that exercise does not increase the risk of MS relapses or adverse events (AEs) relative to control conditions (Pilutti et al., 2014; Learmonth et al., 2023). Collectively, based on an amalgamation of evidence over the past 30 years, exercise training represents an important approach for managing MS manifestations.

As the translation of exercise benefits from the laboratory into MS clinical practice is paramount (Dalgas et al., 2020), safety, adherence and compliance represent major descriptive factors for characterizing the feasibility and fidelity of exercise training interventions. Indeed, the Moving Exercise Research in Multiple Sclerosis Forward (MoXFo) initiative defined safety, adherence, and compliance within the context of RCTs involving exercise training for better informing research and clinical practice (Motl et al., 2023). Based on the MoXFo initiative, safety of exercise programs can be described based on the incidence of AEs; adherence involves attendance of intervention sessions; and compliance involves intervention sessions being completed as prescribed (Motl et al., 2023). Those definitions were agreed upon by an expert panel based on meta-analyses and systematic reviews of RCTs of exercise training in MS. However, those definitions have yet to be applied in RCTs that focus on persons with specific MS-related deficits that could potentially confound safety, adherence, and compliance, such as slowed cognitive processing speed (CPS). Applying the MoXFo criteria for safety, adherence, and compliance within an exercise training intervention in persons with MS who demonstrate slowed CPS is important for moving the field forward, given the emphasis on pre-screening participants for the problem being studied within MS exercise trials (Motl and Sandroff, 2020). Such an application further affords the opportunity to examine potential baseline correlates of adherence and compliance.

To that end, the current study applied the MoxFo framework for characterizing safety, adherence, and compliance (Motl et al., 2023) within a RCT that compared 12-weeks of supervised aerobic treadmill walking exercise (TMWX) training with 12-weeks of supervised stretching and range-of-motion activities as an active control condition in fully-ambulatory persons with MS who were pre-screened for slowed CPS (Sandroff et al., 2019). We further examined baseline correlates of adherence and compliance, as such an endeavor could promote precision medicine by identifying characteristics of persons with MS with slowed CPS that may reflect a higher capacity to complete an exercise prescription as prescribed.

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